The proposed studies are designed to gain a more specific insight into both normal and abnormal mechanisms controlling glucagon and insulin release from the pancreas. Recent evidence indicates that in both juvenile and adult onset diabetes in man, abnormalities exist not only in insulin release, but also in glucagon secretion. Normal mechanisms controlling the release of these two hormones are poorly understood, and it is of elementary importance to define these processes and, subsequently, apply this knowledge to states of abnormal secretion. The proposed studies investigate the basic kinetics of insulin and glucagon secretion, glucose penetration and utilization and the capacity of glucose and other hexoses to serve as fuels for the alpha-cells from the isolated perfused pancreas of normal and diabetic rats.